One atom at a time: The new age of molecular machines

It’s a small world after all — or at least it will be soon. Molecular machines are transforming the way we control motion on the nano-scale. 

Illustration by Andrew Lilja

Illustration by Andrew Lilja

The past few decades have seen an increasing obsession with shrinking technology and machines down in size. In just fifty short years we have gone from the very first computer (ENIAC), weighing in at 27 tonnes, to the MacBook Air, that weighs a little over a kilogram. All around us, from our phones, to tiny transport drones, we see the results of this progress. But we are by no means content with what we have achieved so far.

We have reached the stage where we can engineer machines that are so small, that they can enter the human body and deliver drugs or even perform minute operations. Machines of this size are many orders of magnitude smaller than those we can build by simply reducing the size of machine components. Instead, to construct machines of a molecular size, we must build from the bottom up. Using atoms as our building blocks.

In their simplest form, machines transform energy into motion. Energy cannot be created, nor destroyed, and machines harness this. This is most widely seen as the transformation of chemical energy (such as petrol or food) into kinetic energy (such as a car, or ourselves running). This transformation of energy holds true for molecular machines as well, but is not merely limited to chemical-to-kinetic transformations. Electrical energy, light energy, and heat energy can all be converted into kinetic energy by different molecular motors, allowing a whole range of movements. 

 
ENIAC, the first computer. We’ve come a long way since then, with powerful computers now able to fit inside our pockets. Wikimedia Commons (public domain)

ENIAC, the first computer. We’ve come a long way since then, with powerful computers now able to fit inside our pockets. Wikimedia Commons (public domain)

 

Building molecular machines was not entirely our idea, as it turns out nature is the undisputed master. The reason we are able to live, breathe, and move is due to the workings of amazingly efficient, biological machines within our cells. One of the most important machines found in all life forms, is ATP synthase, a rotational motor enzyme that creates adenosine triphosphate (ATP) — the energy currency of life. The ATP formed by this machine is used as “fuel” by all the other machines (enzymes) found in cells.

One of the enzymes that uses ATP as a fuel is located within our muscles. Our muscles are made up of numerous linear machines, called myosin, that transform the ATP fuel into controlled motion — expansion and contraction. The combination of all these machines expanding and contracting together at a microscopic level, results in our ability to move on a macroscopic scale. These biological machines not only allow us to move, but can also move themselves around cells. Kinesin and dynein are known as ‘walker molecules’, because they transform ATP into controlled motion to move down long tracks and carry cargo around the cell.

 
Walker molecule moving down a track within a cell. Jzp706/Wikimedia Commons (public domain)

Walker molecule moving down a track within a cell. Jzp706/Wikimedia Commons (public domain)

 

Inspired by these amazingly efficient biological machines, many researchers have tried to make their own molecular motors. Like most biomimicry endeavours, this involves recreating the machines we see in the world around us; only on a molecular scale. 

Where better to start than by constructing a nanocar? Developed by James Tour, the nanocar was originally built to merely look like a car — with a central flat ‘chassis’ and round ‘wheels’ coming off the ‘axles’. Unfortunately, like the wooden car (that wooden go), just looking like a car did not mean it functioned like one. According to Dr. James Crowley from the University of Otago, this is because: “the physics of nanoscale machines is different from those of normal-sized everyday macroscopic machines, so we cannot just shrink down cars and planes to the nanoscale and expect them to work in the same way”. 

 
The non-functional nanocar developed by James Tour (back left), a single-engine nanocar, where the engine is embedded in the chassis (back right), and the functional nanocar where the round wheels have been replaced with four rotational engines (front). Image provided by author.

The non-functional nanocar developed by James Tour (back left), a single-engine nanocar, where the engine is embedded in the chassis (back right), and the functional nanocar where the round wheels have been replaced with four rotational engines (front). Image provided by author.

 

With this in mind, a more recent version of the nanocar was produced by Ben Feringa.  The car’s non-functional “wheels” were replaced with four molecular machines capable of rotating in a single direction. This rotational motion is produced by the sequential application of heat and light, transforming radiation into movement. When all four of these engines rotate in unison, the nanocar ‘drives’ forward in a controlled fashion. The next step is to figure out how to load up the nanocar so it can deliver cargo.

While the nanocar could allow transport of cargo across a flat surface from one destination to another, Sir James Fraser Stoddart has built a molecular elevator with a platform that can stop at one of two stations. The elevator uses a chemical fuel (like a car uses petrol or diesel) to move from one state to another. The addition of acid causes the elevator platform to rise to the top station, while adding a base allows the elevator to descend. Although the distance travelled is only 0.7nm, the downward force generated is a staggering 200pN, an order of magnitude greater than the biological machines we rely on in our own bodies. 

 
The shuttling of the molecular elevator platform (red) between two stations (blue and green/pink) on addition of acid and base. Image provided by author.

The shuttling of the molecular elevator platform (red) between two stations (blue and green/pink) on addition of acid and base. Image provided by author.

 

Large contraptions like cars and elevators aren’t the only things that have earned molecular mimics. Takuzo Aida and Kazushi Kinbara have been able to make both molecular scissors and pliers. The scissors use ferrocene — a molecular ball bearing — as a rotatable joint connecting the handles of the scissors to the blades. When different wavelengths of light are shone on the ferrocene, it is capable of opening and closing the blades. By itself, this isn’t particularly useful, but this proof of concept design allowed further development to create molecular pliers. 

The pliers differ from the scissors in that the simple blades have metals embedded within them which are capable of gripping onto a second, separate molecule. Closing the pliers causes the molecule gripped between the blades to be squeezed so that it deforms. This physical transformation of a secondary molecule is an important ability which will allow machine components to be integrated into larger functional ensembles.

 
The opening and closing of the molecular pliers causes deformation of the separate blue molecule gripped between the two blades. The ferrocene ball bearing is depicted in yellow, the handle in light blue, and the metal embedded blade in green/red. Image provided by author.

The opening and closing of the molecular pliers causes deformation of the separate blue molecule gripped between the two blades. The ferrocene ball bearing is depicted in yellow, the handle in light blue, and the metal embedded blade in green/red. Image provided by author.

 

Even though the realisation of fully fledged machines on a molecular scale is amazing, it is difficult to match applications to these specialist motions. Crafting individual machine components that focus on one movement, can be more useful as they can be built up into larger, more functional machines. The creation of a nanovalve to aid in drug delivery (again an example of Sir Stoddart’s work), is a testament to this. 

The nanovalve is a thread-like molecule with a ring that can move between two stations on the thread, much like the molecular elevator. When attached to a porous silica bead, this nanovalve creates a novel drug delivery system that can release drugs on demand with the addition or removal of electrons. In the valve’s open state, a drug can be loaded into the holes in the bead. Removal of electrons from the valve then causes the ring to move down and stopper the holes, locking the drugs inside the bead. Once the bead has reached the site where the drug is needed, the addition of electrons causes the valve to open, and the drug to be released. This, according to Dr. Crowley, is one of the most promising applications of molecular machines, and he expects that “in the next 10-15 years there will be molecular machine based drug delivery systems on the market”.

 
Drug delivery systems can be controlled by nanovalves. The molecular ring (blue) shuttles between the open station (yellow) to the closed station (red) on removal of electrons. In this way, the release of the drug (green) can be controlled. Image provided by author.

Drug delivery systems can be controlled by nanovalves. The molecular ring (blue) shuttles between the open station (yellow) to the closed station (red) on removal of electrons. In this way, the release of the drug (green) can be controlled. Image provided by author.

 

The achievements made in the creation of synthetic molecular machines are impressive, but they still tend to look crude and ineffective when compared to the machines found in biology. Dr. Crowley doesn’t believe this is a terribly fair comparison though, as “nature has had billions of years to develop its machines [while] people have only been trying for the last twenty years”.  

Because it is such a young field, we’re really only testing the waters with simple machine components. We’re still finding out what sort of machine will or won’t work on a molecular scale. Once we’ve mastered the physics of this molecular realm — as we’ve mastered the physics of the macroscopic world around us — the possibilities are endless for the machines we can build. Our only real limit is our imagination.